title: Necrosis and apoptosis of renal tubular epithelial cells in rats exposed to 3-methyl-4-nitrophenol.
abstract: The 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) exists in diesel exhaust particles (DEP), and is also one of the degradation products of insecticide fenitrothion. To assess potential nephrotoxicity of PNMC, male Sprague-Dawley (SD) rats were subcutaneously dosed with PNMC at 1, 10, and 100 mg/kg/day for five consecutive days. No significant changes were detected in body weights and relative weights of kidneys by the treatment of PNMC. However, the extent of cellular necrosis was found to be severe in renal tubular epithelial cells of PNMC-treated rats. In addition, PNMC exposure significantly increased the number of terminal deoxynucleotidyle transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells compared to the control in renal tubule of PNMC-treated rats. Moreover, immunohistochemical results indicated that significant decrease in the B-cell lymphoma 2 (Bcl-2) expressions andincrease in the Bcl-2 associated × protein (Bax) expression were detected in PNMC-treated rats. The ratio of Bcl-2/Bax was also reduced significantly at PNMC-treated rats dosed at 10 or 100 mg kg(-1) . Furthermore, the significant increase of FAS (CD95/APO-1) expression was found in the groups dosed at 10 or 100 mg kg(-1) of PNMC. The expression of Caspase-3 was higher in PNMC-treated rats, compared to the control group. Our results indicated that activation of mitochondria and Caspase-3 protease may contribute to the PNMC-induced apoptosis, suggesting that PNMC could cause both necrosis and apoptosis resulting in cell death of renal epithelium cells and could induce renal toxicity.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yue
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: She
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Bao
authors.forename: Jijing
authors.initials: J
authors.lastname: Tian
authors.forename: Pin
authors.initials: P
authors.lastname: Yu
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhu
authors.forename: Lingling
authors.initials: L
authors.lastname: Chang
authors.forename: Ye
authors.initials: Y
authors.lastname: Ding
authors.forename: Quan
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D003408:Cresols / Q000633:toxicity*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D007684:Kidney Tubules / Q000166:cytology; D008297:Male; D009336:Necrosis / Q000139:chemically induced*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D003408:Cresols; C491898:Fas protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C008636:4-nitro-3-cresol; C505410:Casp3 protein, rat; D053148:Caspase 3